Absence of interferon-λ 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection

Jesper Waldenström, Martin Kåberg, Marianne Alanko Blomé, Anders Widell, Per Björkman, Staffan Nilsson, Anders Hammarberg, Ola Weiland, Kristina Nyström, Martin Lagging

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Absence of a functional interferon-λ 4 (IFN-λ4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods: Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results: The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and ΔGrs1368234815 respectively, p <.001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-λ4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-λ4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p =.006). Conclusions: Absence of IFN-λ4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-λ4, reduced ITPase activity improved outcome.

Original languageEnglish
Pages (from-to)855-861
Number of pages7
JournalScandinavian Journal of Gastroenterology
Volume56
Issue number7
Early online date2021
DOIs
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Infectious Medicine

Keywords

  • acute infection
  • HCV
  • hepatitis C virus
  • IFN-λ4
  • incident infection
  • inosine triphosphate pyrophosphatase
  • Interferon-λ 4
  • ITPA
  • spontaneous clearance
  • spontaneous resolution

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